Morning Seminar
Morning Seminar M2-2

July 4 (Thu) 8:00-8:45 Room 2

Extended One-Generation Reproductive Toxicity Study (EOGRTS- OECD Test Guideline No. 443). The ECHA study design review
project, recommendations and the Future of ED Evaluations
Speaker : Steve Renaut（Associate Director, Developmental and Reproductive Toxicology（DART））
C h a i r : Kazushi Tajima（Sales Director, Crop Protection & Chemicals, Labcorp）
Sponsored by : Labcorp Laboratories Japan K.K.
Overview
A summary of the ECHA review project evaluating the performance of the EOGRTS in terms ofdesign, conduct, analysis, and reporting, and how the results support hazard assessment in the
EU regulatory context. Labcorp will guide you through ECHA critical recommendations, review
project final report and subsequent industry workshop to illustrate how these regulatory
milestones have impacted upon study design. Furthermore, our second topic will cover an
overview of endocrine disruptor assessment in Europe with different endocrine modalities andhow weight of evidence assessments are conducted and impact on classification and labeling.

Morning Seminar M2-4

July 4 (Thu) 8:00-8:45 Room 4

Regulatory Considerations for Nonclinical Safety Evaluation of
New Drugs
Speaker : Dr. Yongbin (Robert) Zhang（Chief Technology Officer & VP，JOlNN Laboratories）
C h a i r : Zheng Yao
Sponsored by : JOINN Laboratories
Overview

Sponsor
Program

1. FDA regulation tips and considerations of new drugs
2. Nonclincial safety considerations of new drugs
3. Case studye91Morning Seminar M3-2

July 5 (Fri) 8:00-8:45 Room 2

Application of Image Analysis and Artificial Intelligence in the
Histology of Pharmaceutical, Chemical and Medical Device Studies
Speaker : Dr. Nils Warfving（AnaPath Services GmbH）
C h a i r : Yoshimasa Okazaki（AnaPath Services GmbH）
Sponsored by : AnaPath Services GmbH
Overview
The history of analyzing images of histological slides is old, but with the rapid technologicaldevelopment of imaging systems, computing power, and artificial intelligence the applications
have become more widespread, and the potential is still growing. In this seminar, I will
highlight numerus examples of classical image analysis and image analysis using more novel
approaches of machine learning and artificial intelligence, using an illustrative approach, in forboth regulatory and exploratory studies in the fields of pharmaceuticals, chemicals and medical
devices.

Morning Seminar M3-3

July 5 (Fri) 8:00-8:45 Room 3

Profiling Genome Editing Outcomes in Human iPS Cell Clones by
CELL HANDLERTM
Speaker : Yuichiro Miyaoka（Regenerative Medicine Project, Tokyo Metropolitan Institute of Medical Science）
C h a i r : Yoshinori Utsumi（New Business Development Center, Medical Device Business Division, Yamaha
Motor Co., Ltd.）

Sponsored by : Yamaha Motor Co., Ltd.
Overview
Grasping outcomes of genome editing in individual cells can be critical for its applications.
Therefore, we analyzed more than 2,600 genome-edited single human cultured cell clones(Takahashi, iScience 25:105619 2022). However, we could not isolate human iPS cell clones
due to their high mortality. Therefore, we have developed a method to efficiently isolate
genome-edited iPS cell clones by CELL HANDLERTM. With this method, we have been able toanalyze genome editing outcomes in more than 1,000 iPS cell clones and found that identicalediting tends to occur in individual human iPS cells.

Sponsor
Programe92

Lunchtime Seminar
Lunchtime Seminar L1-1

July 3 (Wed) 12:00-13:00 Room 1

Current status and issues of pyrogenicity testing
Speaker : Yuji Haishima（Medical Equipment Business Promotion Management Center / Medical YokohamaLab, MIURA CO.,LTD.）C h a i r : Kazuo Miyazaki（CEO, MiCAN Technologies, Inc.）
Sponsored by : MiCAN Technologies, Inc.
Overview
Strict quality control is required for pyrogen contamination in medical products. Pyrogentest with rabbits, endotoxin test and HCPT can be used to evaluate pyrogenicity. Since eachmethod has a different reaction mechanism, advantage and disadvantage, ISO/TR 21582:2021
recommends that appropriate method should be selected according to the purpose of the test.
It is also required to understand the properties of test samples.
In this lecture, classification of pyrogens, characteristics of each test method, and the problems
and solutions regarding current pyrogenicity testing will be outlined.

Lunchtime Seminar L1-2

July 3 (Wed) 12:00-13:00 Room 2①Frontiers in the evaluation of dependence liabilities and harmful
effects of new psychoactive substances and their regulation
Speaker : Masahiko Funada, Professor, PhD（Shonan University of Medical Sciences, Department of Pharmacology）②Comparison of Drug Dependency Testing Guidances in Japan,
Europe and the United States
Speaker : Masahiko Iino（Research Administration Dept., Ina Research Inc.）
C h a i r : Kenichiro Hayashida（Nonclinical Company Drug Safety Research Laboratories, Pharmacology
Department, Associate Director, Shin Nippon Biomedical Laboratories, Ltd.）

Sponsored by : Shin Nippon Biomedical Laboratories, Ltd.

① Health problems arising from abuse of new psychoactive substances (NPS) are an issue inJapan. In order to regulate NPSs, rapid evaluation of dependency and cytotoxicity is vital, anda comprehensive designation for NPSs with similar chemical structure can be an effective tool.
In this seminar, we will introduce conditioned place preference and drug discrimination methods
used to evaluate dependency in mice and a cell culture system used to evaluate cytotoxicity.
We will also talk about the current status of NPS dependency and toxicity evaluation and theprocess of comprehensive designation.
② The Guidelines for Safety Pharmacology Studies (2001) recommend the consideration of"dependency potential" in a section under follow-up studies, and the ICH-M3(R2) Guidance (2010)
states that evaluation of abuse potential should be considered for CNS-active drugs regardlessof indication. Currently, the trilateral regions of Japan, Europe and the United States have eachestablished their own non-clinical guidance for assessing the dependence/abuse potential ofdrugs. In this seminar, we will compare and explain the features of these 3 guidances for drug
dependency testing.

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Sponsor
Program

Overview

Lunchtime Seminar L1-3

July 3 (Wed) 12:00-13:00 Room 3

Moving away from animal models: Organoids and MPS, theforefront of next-generation in vitro models
Speaker : T aro Nakazawa（Molecular Devices Japan KK）
Yoko Ejiri（Mimetas Japan KK）
C h a i r : Koji Udagawa（Molecular Devices Japan KK）
Sponsored by : Molecular Devices Japan KK / Mimetas Japan KK
Overview
Microphysiological Systems (MPS), such as Organ-on-Chip (OOC) and Organoids, are gaining
increasing attention as a new research alternative to animal testing. These technologies cansimulate the in vivo environment and reflect human physiological responses. Mimetas is acompany with a proven history of working with many of the world's leading pharmaceuticalcompanies over the last 10 years. Molecular Devices is working on revolutionary organoid
automation with an AI system that can automatically determine the timing of passaging basedon data. In our seminar, we will present our latest research and innovations in the use oforganoids and OOC.

Lunchtime Seminar L1-4

July 3 (Wed) 12:00-13:00 Room 4

Sense and Nonsense of Bone Marrow Differentiation in Toxicology
Studies
Speaker : D r. Klaus Weber（AnaPath Services GmbH）
Dr. Kristel Kegler（AnaPath Services GmbH）
C h a i r : Yoshimasa Okazaki（AnaPath Services GmbH）
Sponsored by : AnaPath Services GmbH
Overview

Sponsor
ProgramIntroduction: Bone marrow evaluation is a standard component of the toxicologicalinvestigation of routine studies. It involves mainly the routine evaluation of bone marrowsections. Bone marrow differentiation (BMD) is not specifically requested by the guidelines.
It can, however, be a powerful tool in understanding mechanisms of pathogenesis and/or
pharmacological actions.
Experimental Design: The evaluation of bone marrow (BM) sections and the sample
preparation of smears are included in the standard protocols of every regulatory study.
Evaluation of bone marrow smears is not mandatory, but if performed, there are different waysof evaluation including BMD.
Methods: Standard for BMD is the evaluation of smears stained by a May-Grünwald technique.
The number of cells differentiated per smear impacts repeatedly the outcome of the results (i.e.,
200 differentiated cells may cause a 50% variation when a BMD is repeated; whereas, 500
differentiated cells causes a 10% variation when a BMD is repeated). Species, age and sexrelated differences might play a role and need to be known before conducting the BMD (i.e.
control data are helpful in the interpretation of results).
Results: Age-related changes in adult animals are unusual, however, during pregnancy andlactation, females show different BMD values compared to other females of the same age. Side
effects caused by the route of application need to be considered (e.g. inflammatory lesions
due to emboli induced by liposomes). In studies performed with compounds that are previously
known to affect BM (e.g., corticosteroids, platinum compounds, Doxorubicin), BMD could serve
for the setting of thresholds for the applied doses. Similarly, in studies with colony stimulatinge94

factors (e.g., EPO, G-CSF), BMD can demonstrate dose-dependent pharmacological effects andcan also explain adverse side effects at higher doses. For several compounds, BMD can reveal
unique findings involved in the pathogenesis of adverse side effects (e.g., PPAR agonists, alphamethylase inhibitors, lipopolysaccharide, propofol).
Conclusion: Generally, the entire spectrum of lesions recorded in the dose group of interest
needs to be considered together with the BMD results. Every inflammatory or degenerativechange, test item induced or technically related to study procedures, may affect the results.
Further, lesions and measured values of the hematology profile requires consideration. BMD isexpensive and time-consuming and should be well justified before being initiated.
Impact Statement: The isolated diagnostic on either bone marrow sections or bone marrowsmears may cause misinterpretation or even misdiagnosis. BMD may be an interesting tool for
threshold effects, and, for some compounds, it might explain the pathogenesis of side effects.

Lunchtime Seminar L1-5

July 3 (Wed) 12:00-13:00 Room 5

Use of virtual control groups in nonclinical developmental,
reproductive, and juvenile toxicity studies: are we ready yet?
Speaker : Elise M. Lewis, Ph.D.（Principal Director, Toxicology, Charles River）
C h a i r : Sayaka Odagriri（DSA SCIENTIFIC）
Sponsored by : Charles River
Overview
As nonclinical scientist, we have a responsibility not only to align with the 3Rs in animal-based
research, but we must exercise responsible use of animals in our research practices. Virtual
control groups have emerged as a tool with the promise of reducing animal use by replacing
control group animals with virtual counterparts in nonclinical studies, where feasible. For
developmental, reproductive, and juvenile toxicology, the conversation starts today. How do
we advance as a community towards 21st century thinking and reduce, eliminate, or consider
alternative approaches to facilitate data comparisons and interpretation through other means
such as historical control data warehouses?

Lunchtime Seminar L1-6

July 3 (Wed) 12:00-13:00 Room 6

Exploring the Potential Application of Natural Language
Processing AI to the Field of Safety Evaluation

Sponsor
ProgramSpeaker : Makoto Miyamoto（Director, Lifescience AI Research Team, FRONTEO, Inc.）
C h a i r : Hiroyoshi Totoshiba（Executive Officer CTO, FRONTEO, Inc.）
Sponsored by : FRONTEO, Inc.
Overview
FRONTEO has developed its own natural language processing (NLP) AI engine, "KIBIT," andhas already used it for novel drug target discovery, drug repositioning, biomarker discovery,
their hypothesis generation, etc. The use of NLP technology in the field of toxicity, as well as
in target discovery, would be useful for predicting and understanding clinical safety. Currently,
the use of NLP technology in safety prediction/evaluation is still progressing. Therefore, in thisseminar, we focus on drug safety evaluation and explore the effectiveness of using KIBIT in thesafety assessment process.

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Lunchtime Seminar L1-7

July 3 (Wed) 12:00-13:00 Room 7

Best Practices and Challenges in Avian and Aquatic Toxicology
Testing
Speaker : S uzanne Z. Schneider, Ph.D（Associate Director of Aquatic Toxicology, Eurofins-Easton）
Patrick Hubbard, B.S.（Senior Scientist Avian Toxicology, Eurofins-Easton）
C h a i r : Satoshi Furukawa, PhD, DVM, DJSOT, DJSTP, DJCVP, FIATP（Nissan Chemical Corporation）
Sponsored by : Eurofins EAG Agroscience
Overview
This seminar will cover the following topics that Eurofins Easton conducts.
1. A vian toxicology studies: overview including hen metabolism and residue studies, andchallenges faced.
2. Endocrine disruptor screening program
i. Tier 1 screening: best practiceii. Tier 2 assays: overview of MEOGRT and LAGDA and challenges faced.
3. Panel discussion: emerging technologies and regulatory updates that might impact testing
for registration.

Lunchtime Seminar L2-2

July 4 (Thu) 12:00-13:00 Room 2①Imitation of in-vivo environment using multi-organ MPS“HUMIMIC”
Speaker : Hideo Takeda（PHYSIO MCKINA Co., Ltd.）C h a i r : Chihiro Imai（PHYSIO MCKINA Co., Ltd.）②Confocal Imaging of 3D Biological Tissue Using the HUMIMIC Chip
Speaker : Tetsuomi Takasaki（Nikon Solutions Co., Ltd.）C h a i r : Kenji Miyamoto（Nikon Solutions Co., Ltd.）
Sponsored by : PHYSIO MCKINA Co., Ltd. / NIKON SOLUTIONS CO., LTD.
Overview

Sponsor
Program① When I talked to researchers who wanted to use MPS to imitate the in-vivo environment, I
realized that their goals varied greatly depending on the researcher.Therefore, in this seminar,
I will provide an overview of why MPS is attracting attention, what MPS can do, and global
trends, using TissUse's multi-organ MPS ""HUMIMIC"" as an example.
② An observation example of TissUse’s HUMIMIC Chip with Nikon’s confocal microscope
Eclipse Ti2E-AX will be introduced in this seminar. The HUMIMIC Chip has the characteristicof being able to co-culture multiple organoids. As an example, results of image acquisition
regarding 3D culture samples of the intestine and bone marrow will be introduced. The cells’
polarity was confirmed by observation of the tight junction marker ZO-1 with the intestine
model, and then, growth of the elongated MSCs expressing F-actin and circular HSCs wasobserved in the confocal images of the bone marrow model. In addition, the tissue-specificthree-dimensional morphology and localization of markers were successfully observed with
Ti2E-AX. The bone marrow model is expected to be used in Toxicity assessment of long-term
administration of anticancer drugs, then contribute to drug discovery research as one of thealternative tools to animals.

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Lunchtime Seminar L2-3

July 4 (Thu) 12:00-13:00 Room 3

Validation of a Zebrafish Developmental/Teratogenic Assay as
a Qualified New Alternative Method (NAM) for its Regulatory use
following the ICH S5(R3) Guideline
Speaker : Arantza Muriana（Co-founder, R&D Director, and CEO of USA, BBD BioPhenix S.L.U（Biobide））
C h a i r : Kazuhiro Shimomura, PhD（DAIICHI SANKYO CO., LTD. Vaccine Research Laboratories
Group II, R&D Division）

Sponsored by : BioBide (BBD BIOPHENIX S.L.U.) / BioSafety Research Center Inc.
Overview
The ICH S5 (R3) Guideline on detection of reproductive and developmental toxicity of humanpharmaceuticals, in its 2020 review proposes the use of new alternative methods (NAMs) as
part of an integrated testing strategy to minimize the use of animals. The guideline provides alist that contains 29 positive compounds that have been shown to induce specific malformations
or embryo-fetal lethality, plus 3 negative compounds to be used to support the qualification ofan alternative assay.
Our research was focused on the predictivity of the zebrafish developmental toxicity
assay. The Zebrafish embryo model is highly popular in toxicology and provides an ethically
acceptable small-scale analysis system with the complexity of a complete organism. This model
enables continuous developmental monitoring and has been widely used for the generation of
relevant answers on mammalian developmental hazards. Our goal was to validate this model
for its regulatory use by testing the 32 compounds indicated in the ICH S5(R3) Guideline.
To determine the teratogenic risk of these pharmaceuticals, the presence of morphologicalalterations was analyzed at two different stages and the Teratogenic Indexes established as
the ratio between LC50 and EC50 for each stage.
The 32 compounds were screened in the zebrafish developmental toxicity assay. 23 outof the 29 reference compounds were classified as teratogenic in zebrafish, 6 of them werefalse negatives initially, 4 were classified as inconclusive, 1 was classified as not toxic, and 1
compound resulted toxic for zebrafish embryos under the testing conditions.

Lunchtime Seminar L2-4

July 4 (Thu) 12:00-13:00 Room 4

Case study of IND enabling toxicity study in KI animals and recent
topic of FDA/CBER
Speaker : Hideo Fukui（Science Strategy & Planning, Axcelead Drug Discovery Partners, Inc.）
C h a i r : Hisaharu Yamada（Corporate Strategy Div., Mediford Corporation / Faculty of Pharmaceutical
Sciences, Tokyo University of Science）

Sponsored by : Axcelead Drug Discovery Partners, Inc / Mediford Corporation
Overview
Regulatory authorities require non-clinical safety studies of new modality drugs and small
molecule drugs to evaluate on-target and off-target toxicity. In particular, monkeys are often

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Sponsor
Program

The bioavailability analysis performed after the teratogenicity assay allowed the classifying
properly several of the inconclusive compounds, increasing accuracy of the assay to 89.66%,
sensitivity to 88.46%, and specificity and repeatability being 100%, compared to rodents
and rabbits. Therefore, this is a well-integrated approach using New Alternative Methods tominimize the use of animals in developmental toxicity studies.

selected as a non-clinical animal species in new modality medicines. However, due to the highprice of monkeys and import restrictions, it is difficult to conduct non-clinical studies, and it
seems that the progress of many projects in Japan and overseas has been affected. Recently,
successful cases of switching to toxicity studies using KI animals have begun to be disclosed.
The case study and the recent topic of the FDA/CBER will be introduced.

Lunchtime Seminar L2-5

July 4 (Thu) 12:00-13:00 Room 5

Early de-risking and prediction of human safety in drug discovery
Speaker : Paul Walker Ph.D.（VP Head of Toxicology and Innovation Efficiency）
C h a i r : Masaaki Yatsu（Authorized Agent, Cyprotex Discovery Limited）
Sponsored by : Cyprotex Discovery Limited
Overview
We present in vitro approaches and associated safety cascades to de-risk small chemical
entities (NCEs) in early drug discovery. Using in vitro models of human relevance such as
human liver microtissues (hLiMTs) and cardiac tri-culture organoids. Human safety prediction
is determined with combining these in vitro models with 3D high content imaging (HCI) and fullgenome transcriptomics (Tx).
AI/ML models are utilised to determine a human safety risk
profile.

Lunchtime Seminar L2-6

July 4 (Thu) 12:00-13:00 Room 6

Unlocking the Power of AI and Advanced Analytics for DataDriven Decision Making in Drug Safety:
A Case Study with Unstructured and Structured Safety Data in
PharmaPendium
Speaker : Thomas Vargues（Elsevier）
C h a i r : Takahiro Ohyama（Elsevier Japan）
Sponsored by : Elsevier Japan K. K.
Overview

Sponsor
Program

The pharmaceutical industry generates vast amounts of safety data from various sources,
including clinical trials, post-marketing surveillance, and regulatory submission (FDA, EMA,
PMDA) documents. However, much of this data is unstructured (labels, full packages, advisorycommittee reports etc…) and difficult to analyze, making it challenging to identify potential
safety issues and make informed decisions. In this talk, we will explore how AI and advanced
analytics can be used to unlock the power of unstructured and structured safety data in
PharmaPendium for data-driven decision making in drug safety. We will discuss how AI
techniques, such as natural language processing (NLP) and retrieval augmented generation(RAG), can be used to analyze unstructured regulatory documents and extract safety-related
information to improve safety monitoring and compliance with regulatory requirements.
Additionally, we will explore how structured safety data in PharmaPendium, such as safety
related adverse drug reactions (ADRs) data and pharmacokinetic data, can be analyzed using
advanced analytics and visualization to optimize drug development strategies and prioritize
safety testing efforts.

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Lunchtime Seminar L2-7

July 4 (Thu) 12:00-13:00 Room 7

1. The New Approach for Carcinogenic Evaluation — Accumulate
More Information for Weight of Evidence in Early Stage of Drug
Discovery
Speaker : Chun-Yao Lee, Ph.D.（Director of Molecular Pharmacology, Managing Director, Eurofins Discovery Taiwan）

2. Can We Better Predict Potential Drug Toxicity Using the
BioMAP® Translational Biology Platform to Help Reduce
Attrition or Withdrawal?
Speaker : Alastair J. King, Ph.D.（Head of Biology, Eurofins Discovery）
C h a i r : Makoto Imatachi（Regional Director of Business Development Japan/Korea, Eurofins Discovery）
Sponsored by : Eurofins Discovery
Overview
1. ICH S1B (R1) guidance introduces a Weight of Evidence (WoE) approach using varietiesof evidence—in vitro, in vivo, and clinical data to assess carcinogenic potential. Oncogenic
responses are triggered by chemical exposure via inflammation, immune modulation, andcellular damage, which led Eurofins Discovery to develop a panel integrating 30 key targets
to assess mechanisms and identify non-genotoxic carcinogens. In addition to this, a Cell
Transformation Assay has been developed to evaluate carcinogen-induced malignant
phenotypes, incorporating an AI-based image analysis module to improve objectivity. In vitro
assays as alternatives to animal modeling remain crucial tools for understanding and mitigating
carcinogenic risk.
2. Despite the availability of many robust, well-qualified in vitro safety and toxicity assays, drug
failure in clinical testing due to unanticipated toxicity is still disappointingly high. However,these assays do not sufficiently model the human body’s intricate biology well enough tomore reliably predict such adverse outcomes. We will discuss the use of complex cell coculture models and data analytics to identify potential toxicity signatures in a translational andclinically relevant in vitro platform. This will be highlighted using case studies with approved
and withdrawn drugs, to illustrate how a reduction in the occurrence of unforeseen toxicities
could lower attrition and withdrawal.

Lunchtime Seminar L3-1

July 5 (Fri) 12:10-13:00 Room 1

Sponsor
Program

New Method for Calculating Safety Margin in Cardiovascular
Safety Evaluation per New ICH S7B Guideline Q&As
Speaker : Atsushi Sugiyama（Department of Pharmacology, Faculty of Medicine, Toho University;
Yamanashi Research Center of Clinical Pharmacology）

Hiroshi Matsukawa（Kashima laboratories, Mediford Corporation）
C h a i r : Hideomi Uchida（Kashima laboratories, Mediford Corporation）
Sponsored by : Mediford Corporation
Overview
Drug-induced cardiotoxicity is a major concern in drug development, necessitating reliabledata for appropriate cardiovascular safety assessment. In recent years, the newly developed
ICH S7B Guideline Q&As, which address the evaluation of adverse effects of drugs on the
cardiovascular system critical for life support, have provided best practices for integrated
clinical and non-clinical risk assessment, significantly transforming the ways of conducting

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cardiovascular assessment. In the first half of the seminar, we will explain the evolution fromthe latest ICH S7B Q&As Stage 1 to Stage 2 and the evaluation of anticancer agents. In thesecond half, we focus on the hERG assay, which plays a central role in in vitro assessments,
and present the work we have been conducting. In addition to actual methods for dataacquisition and analysis with reference drugs (moxifloxacin, ondansetron and dofetilide), we
provide details on how to calculate the hERG safety margin associated with a 10 ms QTc
prolongation and pooled safety margin, both of which have attracted considerable interest(submitted).

Lunchtime Seminar L3-2

July 5 (Fri) 12:00-13:00 Room 2①Human hepatocytes usable for the industrial implementation of
microphysiological systems
Speaker : Seiichi Ishida（Division of Applied Life Science, Graduate School of Engineering, Sojo University）②Mitigation strategy of drug-induced liver toxicity by utilizing
PXB-cells in lead optimization stage
Speaker : Tomoya Yukawa（Takeda pharmaceutical company limited, Research, Drug Safety Research and Evaluation）
C h a i r : Tatsuya Matsumi（PhoenixBio Co., Ltd.）
Sponsored by : PhoenixBio Co., Ltd.
Overview
Dr. Seiichi Ishida, Sojo University, and Dr. Tomoya Yukawa, Takeda Pharmaceutical Company
will present examples of hepatotoxicity evaluation using fresh human hepatocytes (PXB-cells)
isolated from the chimeric mice with humanized liver.

Lunchtime Seminar L3-3

July 5 (Fri) 12:00-13:00 Room 3

Collaborating with CROs: The Prospects of Novel Medical
Research Enabled by Bio 3D Printing
Speaker : Shizuka Akieda（CEO, Cyfuse Biomedical K.K.）
C h a i r : Mayumi Kano（Sales Planning Department, Nihon Bioresearch Inc.）
Sponsored by : Nihon Bioresearch Inc.
Overview
Sponsor
Program

In recent years, regenerative medicine and drug discovery research has accelerated using
Bio 3D printing technology. In the field of regenerative medicine, 3D tissue is being used intransplantation, and in the field of drug discovery, its use as a tool for evaluating the kinetics
and efficacy of drugs is accelerating.
3D tissues of Cyfuse are created using only cells, and clinical trials for nerve, cartilage, bloodvessel regeneration, etc. are being conducted. Additionally, Cyfuse has initiated the sale ofhuman 3D mini livers for drug discovery.
We would like to introduce our partnership strategy and product development with NBR, frombasic research to clinical development to commercialization.

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Lunchtime Seminar L3-4

July 5 (Fri) 12:00-13:00 Room 4

Mycobacterium caprae infection in imported laboratory
Cynomolgus macaques (Macaca fascicularis ): what have welearned from diagnosis and management from an outbreak causedby an emerging mycobacterial species?
Speaker : D r. Kristel Kegler（AnaPath Services GmbH）
Dr. Klaus Weber（AnaPath Services GmbH）
C h a i r : Yoshimasa Okazaki（AnaPath Services GmbH）
Sponsored by : AnaPath Services GmbH
Overview
Emerging mycobacterial species causing tuberculosis (TB) are a major challenge for diagnosis
and surveillance. Here we present a natural outbreak caused by Mycobacterium caprae inimported cynomolgus macaques (Macaca fascicularis ) occurring at AnaPath Research S.A.U.
(APR). Despite repetitive Intradermal Tuberculin Test (IDT) at the breeding farm and European
quarantine station, 10 out of 114 animals had gross and histologic findings compatible with
TB confirmed by PCR and culture, and 4 animals had early infection diagnosed only byhistopathology. Affected were three regulatory toxicity studies and stock animals, and one
worker had positive IDT reaction. M. caprae spoligotype SB1622 was identified tracing theinfection to Asia. Diagnostic approaches used at APR including IDT, Interferon-γ release assay,
and ultrasound were sensitive in detecting chronic-active cases but failed to identify early
infection. Histologically, M. caprae induces a distinctive type of granuloma characterized bylack of capsule with high rate of rupturing into airways, and presence of a specific populationof spindle cells forming glomeruloid-like structures at the periphery of the granuloma.
Metagenomics used to identify possible co-infection with bacteria or viruses aiming to explainthese characteristic features failed to demonstrate any concomitant microorganism. Hence,solely infection with M. caprae elicits a distinctive type of granuloma with high transmission
potential. Nonetheless, all sanitary measures implemented were effective in eradicating thedisease at the facility.

Lunchtime Seminar L3-5

July 5 (Fri) 12:00-13:00 Room 5

Addressing Unmet Needs for Reproductive, Developmental, andJuvenile Toxicology Testing using Advanced Therapies andTechnologies
Sponsor
ProgramSpeaker : Elise M. Lewis, Ph.D.（Principal Director, Toxicology, Charles River）
C h a i r : Hiroyuki Minami, Ph.D.（DSA SCIENTIFIC）
Sponsored by : Charles River
Overview
The field of developmental, reproductive, and juvenile toxicology have evolved over decades
to allow scientists and clinicians to address unmet needs that stem from inborne errors indevelopment. Though the ICH guidelines pertaining to reproductive, developmental, and juvenile
toxicity explicitly excludes cellular therapies, gene therapies, and tissue-engineered products
from the testing guidelines, the safety of these products must be addressed in nonclinicalsettings to ensure efficacy and patient safety. To meet future needs we are realizing that theunderstanding the molecular basis of drug interactions with the developing embryo will allow us
to better predict the hazard from exposure.

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Lunchtime Seminar L3-6

July 5 (Fri) 12:00-13:00 Room 6

The cynomolgus macaque in nonclinical safety testing: Relevanceof animal origin and insights into intrathecal dosing of antisenseoligonucleotides
Speaker : Lars Mecklenburg, DVM, PhD, DACVP, FIATP（Executive Director,Global Safety
Assessment, Labcorp Early Development）

C h a i r : Michiko Fukuda（Business Development Director / Early Development, Labcorp）
Sponsored by : Labcorp Laboratories Japan K.K.
Overview
Cynomolgus macaques are the predominant species for nonclinical safety testing of
biopharmaceuticals. The recent shortage in animal supply urges to optimize their use. This
presentation reviews the impact of geographical animal origin in relation to selected endpoints
that are relevant in nonclinical safety testing. The presentation will also discuss intrathecal
dosing in macaques as an increasingly common route of administration for antisense
oligonucleotides that target central nervous system diseases. We present typical clinicalobservations and pathology findings in such studies and explain their relevance in preclinicalsafety testing.

Lunchtime Seminar L3-7

July 5 (Fri) 12:00-13:00 Room 7

Support for Life Science and Drug Discovery Research by AMEDBINDS and Utilization of Incucyte® at the Center for Supporting
Drug Discovery and Life Science, Osaka University
Speaker : Kazutake Tsujikawa（Graduate School of Pharmaceutical Sciences, Osaka University）
C h a i r : Shohei Shimonishi（Sartorius Japan K.K.）
Sponsored by : Sartorius Japan K.K.
Overview

Sponsor
Program

AMED Basis for Supporting Innovative Drug discovery and life Science research (BINDS) is
a research support program that aims to link the results of Japan's outstanding life science
research to drug discovery research. The Center for Supporting Drug Discovery and Life
Science. Grad. Sch. Pharm. Sci., Osaka University has been selected for BINDS and has
established a system to seamlessly support life science and drug discovery research. In
this seminar, I will introduce our BINDS support system as well as examples of Incucyte®'sutilization in toxicity evaluation using spheroids and organoids.

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